Microsomes bound

Figure 22-3. Transport and hepatic metabolism of bilirubin. Bilirubin that is produced in phagocytes is transported to liver as an albumin-bilirubin complex. Uptake into the hepatocytes takes place in liver sinusoids. Within the hepatocyte, bilirubin is transported to the endoplasmic reticulum (microsomes) bound to glutathione S-transferase (GST). Bilirubin is made water soluble by addition of one or two glucuronic acid moieties obtained from UPD-glucuronic acid, catalyzed by bilirubin-UDP-glucuronyltransferase. The product, conjugated bilirubin, is transported across the bile canalicular membrane for secretion into the biliary system, with subsequent movement into the intestines.

Feeding rats cholesterol or cholestyramine alters both the and the Arrhenius activation energies for microsomally bound, but not for solubilized, HMG-CoA reductase [198]. 

Participation of SCPj in the conversion of enzymatically generated, microsome-bound squalene to sterol... 

Fig. 1. Conversion of microsome-bound [ CJsqualene to sterol as a function of partially purified SCP, concentration. Microsome-bound [ CJsqualene was enzymatically generated from [1,5,9- CJfarnesyl pyrophosphate [23]. Additional experimental details are described in ref. 24.

These results demonstrate that SCP2 participates in the microsomal conversion of cholesterol to cholesterol ester. It is quite possible that SCP2 participates in the delivery of either exogenous (dietary) or endogenous (microsomally bound) cholesterol to ACAT which is bound to the endoplasmic reticulum. 

Mevinolin radish seedlings, microsome-bound 2.2 Bach Lichtenthaler 1983 (53)... 

Squalene epoxidase, like most enzymes responsible for the later steps of sterol biosynthesis [43, 51], is membrane-bound which makes its purification in native form challenging. The purification is additionally complicated by the presence of a large number of cytochrome P450 and other enzymes that have similar hydro-phobicity and size as squalene epoxidase and are hence difficult to remove [52]. Most studies have been carried out with rat liver microsome squalene epoxidase either partially purified or as a homogenate of the cell membrane fraction. In vitro reconstitution of squalene epoxidase activity is absolutely dependent on molecular oxygen, NADPH, FAD, and NADPH-cytochrome c reductase [52, 53]. In this respect, squalene epoxidase resembles the cytochrome P450 enzymes described... 

Two important examples of reductive metabolism of xenobiotics are the reductive dehalogenation of organohalogen compounds, and the reduction of nitroaromatic compounds. Examples of each are shown in Figure 2.13. Both types of reaction can take place in hepatic microsomal preparations at low oxygen tensions. Cytochrome P450 can catalyze both types of reduction. If a substrate is bound to P450 in the... 

Two forms of this enzyme are known, a membrane-bound form mainly found in microsomes of all cells and a soluble form present in red blood cells. Structurally, the soluble form with 275 amino acid residues lacks a hydrophobic segment at the NH2 terminus which is present in the membrane-bound enzyme with 300 amino acid residues. Both isoforms are produced by a single gene on chromosome 22 (T17,Y4). 

The coupling of solute transport in the GI lumen with solute lumenal metabolism (homogeneous reaction) and membrane metabolism (heterogeneous reaction) has been discussed by Sinko et al. [54] and is more generally treated in Cussler s text [55], At the cellular level, solute metabolism can occur at the mucosal membrane, in the enterocyte cytosol, and in the endoplasmic reticulum (or microsomal compartment). For peptide drugs, the extent of hydrolysis by lumenal and membrane-bound peptidases reduces drug availability for intestinal absorption [56], Preferential hydrolysis (metabolic specificity) has been targeted for reconversion... 

The search for an alternative reactive metabolite for the polycyclic hydrocarbon carcinogens was soon successful. Also in 1973, Borgen et al. (54) reported that, in the presence of a microsomal system from hamster liver, trans 7,8-dihydro-7,8-dihydroxybenzola]-pyrene (a metabolite of benzo[aJpyrene) was bound to DNA in vitro some ten times more extensively than was benzo[a]pyrene itself. 

Ji,Y., Akerboom,T.P.M., Sies, H., Microsomal formation of S-nitrosoglutathione from organic nitrites possible role of membrane-bound glutathione transferase. Biochem. J. 313 (1996), p. 377-380... 

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